Derivatives of heterocycles with 5 members, their preparation and their use as medicaments

Abstract

The invention relates to thiazole, oxazole, imidazole, isoxazole and isoxazoline derivatives of general formula (I) wherein Het is thiazole, oxazole, imidazole, isoxazole or isoxazoline, n is an integer from 0 to 6, A is notably selected from various optionally substituted aromatic radicals, B is notably hydrogen, alkyl or phenyl, R 1 and R 2 are notably independently hydrogen, alkyl or cycloalkyl and Ω is —NR 46 R 47 or —OR 48 , R 46 and R 47 are notably independently hydrogen, alkyl, cycloalkyl or —(CH 2 ) k —COOR 51 , R 51 is notably alkyl or haloalkyl and R 48 is notably hydrogen or alkyl. These compounds have advantageous pharmacological properties which allow their use in therapeutics, notably for treating neurodegenerative disorders or pain.

1. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a compound of the formula 
       
         
           
           
               
               
           
         
         in racemic, enantiomeric form or any combination of these forms, in which Het is a heterocycle with 5 members comprising 2 heteroatoms and such that formula (I) G  is: 
       
       
         
           
           
               
               
           
         
         in which 
         A is 
       
       
         
           
           
               
               
           
         
         in which Q is —OR 22  and R 22  is hydrogen 
         and R 19 , R 20  and R 21  are hydrogen or alkyl, 
         X is —S—, 
         R 1  and R 2  are hydrogen or alkyl, 
         B is hydrogen, 
         Ω is NR 46 R 47 , 
         R 46  and R 47  are hydrogen or alkyl, 
         n is an integer from 0 to 6; 
         or its pharmaceutically acceptable salts. 
       
     
     
       2. The pharmaceutical composition of  claim 1 , wherein n is an integer from 0 to 2. 
     
     
       3. The pharmaceutical composition of  claim 2 , wherein R 1  and R 2  are hydrogen. 
     
     
       4. The pharmaceutical composition of  claim 2 , wherein R 1  is hydrogen and R 2  is alkyl. 
     
     
       5. The pharmaceutical composition of  claim 1 , wherein n is 0. 
     
     
       6. A pharmaceutical composition comprising 4-[2-(aminomethyl)-1,3-thiazol-4-yl]-2,6-di(tert-butyl)phenol or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient. 
     
     
       7. The pharmaceutical composition of  claim 2 , wherein the compound is 4-[2-(aminomethyl)-1,3-thiazol-4-yl]-2,6-di(tert-butyl)phenol or its pharmaceutically acceptable salt. 
     
     
       8. The pharmaceutical composition of  claim 1 , wherein the compound is 4-{2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol or its pharmaceutically acceptable salt. 
     
     
       9. A pharmaceutical composition comprising 4-{2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient. 
     
     
       10. A method of inhibiting monoamine oxidase and/or lipidic peroxidation in warm-blooded animals comprising administering to warm-blooded animals in need thereof an amount of a compound of the formula 
       
         
           
           
               
               
           
         
         in racemic, enantiomeric form or any combination of these forms, in which Het is a heterocycle with 5 members comprising 2 heteroatoms and such that general formula (I) G  is: 
       
       
         
           
           
               
               
           
         
         in which A is 
       
       
         
           
           
               
               
           
         
         in which Q is OR 22  and R 22  is hydrogen; 
         and R 19 , R 20  and R 21  are hydrogen or alkyl; 
         X is S; 
         R 1  and R 2  are hydrogen or alkyl; 
         B is hydrogen, 
         Ω is NR 46 R 47 , and R 46  and R 47  are hydrogen or alkyl; 
         n is an integer from 0 to 6; or its pharmaceutically acceptable salts. 
       
     
     
       11. The method of  claim 10 , wherein n is an integer from 0 to 2. 
     
     
       12. The method of  claim 11 , wherein R 1  and R 2  are hydrogen. 
     
     
       13. The method of  claim 11 , wherein R 1  is hydrogen and R 2  is alkyl. 
     
     
       14. The method of  claim 10 , wherein n is 0. 
     
     
       15. The method of  claim 10 , wherein two of R 19 , R 20  and R 21  represent an alkyl and the third hydrogen. 
     
     
       16. The method of  claim 10 , wherein the compound is 4-[2-(aminomethyl)-1,3-thiazol-4-yl]-2,6-di(tert-butyl)phenol or its pharmaceutically acceptable salt. 
     
     
       17. The method of  claim 10 , wherein the compound is 4-{2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol or its pharmaceutically acceptable salt. 
     
     
       18. The pharmaceutical composition of  claim 1 , wherein two of R 19 , R 20  and R 21  represent an alkyl and the third hydrogen.